title: Cell-penetrating fusion peptides OD1 and OD2 interact with Bcr-Abl and influence the growth and apoptosis of K562 cells.
abstract: The Bcr-Abl oncoprotein is the cause of chronic myelogenous leukemia (CML). Crystal structure analysis suggests that Bcr30-63 is the core of the Bcr-Abl oligomerization interface for aberrant kinase activity; however, the precise role of other residues of Bcr1-72 excluding Bcr30-63 have not been evaluated. In this study, Bcr30-63 was named OD2 and other residues of Bcr1-72 were named OD1. Cytoplasmic transduction peptide (CTP) was used to carry molecules into cytoplasm. CTP-OD1 and CTP-OD2 fusion peptides were expressed from a cold-inducible expression system. Our results demonstrated that both fusion peptides could localize into the cytoplasm, specifically interact with the Bcr-Abl protein and further inhibit growth, induce apoptosis, and decrease the phosphorylation of Bcr-Abl in K562 cell lines. However, the viability of THP-1, a Bcr-Abl negative cell line, was unaffected. These results suggested that CTP-OD1 and CTP-OD2 may be an attractive therapeutic option to inhibit the activation of Bcr-Abl kinase in CML.
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, Department of Clinical Hematology, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Wang
authors.forename: Heng
authors.initials: H
authors.lastname: Xiao
authors.forename: Liang
authors.initials: L
authors.lastname: Zhong
authors.forename: Kun
authors.initials: K
authors.lastname: Tao
authors.forename: Ya-Juan
authors.initials: YJ
authors.lastname: Li
authors.forename: Shi-Feng
authors.initials: SF
authors.lastname: Huang
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Wen
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Feng
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D057075:Enzyme Assays; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D020014:K562 Cells; D011485:Protein Binding / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D057846:Cell-Penetrating Peptides; D011993:Recombinant Fusion Proteins; D016044:Fusion Proteins, bcr-abl